Pro-apoptotic effect of the c-Abl tyrosine kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine

被引：42

作者：

Huang, YY ^{[1
]}

Yuan, ZM ^{[1
]}

Ishiko, T ^{[1
]}

Nakada, S ^{[1
]}

Utsugisawa, T ^{[1
]}

Kato, T ^{[1
]}

Kharbanda, S ^{[1
]}

Kufe, DW ^{[1
]}

机构：

[1] HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CANC PHARMACOL, BOSTON, MA 02115 USA

来源：

ONCOGENE | 1997年 / 15卷 / 16期

关键词：

ara-C; c-Abl kinase; apoptosis; p53;

D O I：

10.1038/sj.onc.1201376

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Treatment of cells with the antimetabolite 1-beta-D-arabinofuranosylcytosine (ara-C) and other genotoxic agents is associated with activation of the c-Abl protein tyrosine kinase. The functional role of c-Abl in the response to DNA damage, however, remains unclear. The present studies demonstrate that cells expressing a dominant negative, kinase-inactive c-Abl (K-R) are resistant to killing by ara-C. The expression of c-Abl (K-R) blocked ara-C-induced apoptosis by a mechanism that is at least in part independent of the p53 tumor suppressor. Cells null for c-Abl also exhibited resistance to induction of apoptosis. These findings provide support for a pro-apoptotic function of c-Abl in the response to certain genotoxic drugs.

引用

页码：1947 / 1952

页数：6

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